TY - JOUR
T1 - High von Willebrand factor levels increase the risk of first ischemic stroke -
T2 - Influence of ADAMTS13, inflammation, and genetic variability
AU - Bongers, Tamara N.
AU - de Maat, Moniek P. M.
AU - van Goor, Mary-Lou P. J.
AU - Bhagwanbali, Vinod
AU - van Vilet, Huub H. D. M.
AU - Garcia, Encarna B. Gomez
AU - Dippel, Diederik W. J.
AU - Leebeek, Frank W. G.
PY - 2006/11
Y1 - 2006/11
N2 - Background and Purpose-Elevated von Willebrand factor (vWF) concentrations are associated with an increased risk of ischemic heart disease. Several factors influence vWF antigen levels and activity, including blood group, genetic variability, acute-phase response, and proteolysis by A Disintegrin and Metalloprotease with ThromboSpondin motif (ADAMTS 13), a determinant of proteolytic cleavage of vWF. We assessed how these factors affect the relation between vWF and the occurrence of stroke to understand the underlying mechanism.Methods-In a case-control study of 124 first-ever ischemic stroke patients and 125 age- and sex-matched controls, we studied vWF antigen (vWF:Ag), vWF ristocetin cofactor activity (vWF:RCo), ADAMTS13 activity, the -1793C/G polymorphism in the vWF gene, and C-reactive protein.Results-vWF antigen and activity levels were significantly higher in cases than in controls. The relative risk of ischemic stroke was highest in individuals in the upper quartile of vWF:Ag (odds ratio, 3.2; 95% CI, 1.4 to 7.5) and vWF:RCo (odds ratio, 2.1; 95% CI, 0.9 to 4.8) compared with individuals in the lowest quartiles. In individuals with ADAMTS 13 in the lowest quartile, the relative risk of stroke was 1.7 (95% CI, 0.7 to 3.9) compared with the highest quartile. C-reactive protein, ADAMTS 13, and genetic variation did not affect the association between vWF and the relative risk of stroke, whereas blood group did affect the association.Conclusions-vWF antigen and activity are associated with the occurrence of acute ischemic stroke. This relation is unaffected by the severity of the acute-phase response or by genetic variation or degradation.
AB - Background and Purpose-Elevated von Willebrand factor (vWF) concentrations are associated with an increased risk of ischemic heart disease. Several factors influence vWF antigen levels and activity, including blood group, genetic variability, acute-phase response, and proteolysis by A Disintegrin and Metalloprotease with ThromboSpondin motif (ADAMTS 13), a determinant of proteolytic cleavage of vWF. We assessed how these factors affect the relation between vWF and the occurrence of stroke to understand the underlying mechanism.Methods-In a case-control study of 124 first-ever ischemic stroke patients and 125 age- and sex-matched controls, we studied vWF antigen (vWF:Ag), vWF ristocetin cofactor activity (vWF:RCo), ADAMTS13 activity, the -1793C/G polymorphism in the vWF gene, and C-reactive protein.Results-vWF antigen and activity levels were significantly higher in cases than in controls. The relative risk of ischemic stroke was highest in individuals in the upper quartile of vWF:Ag (odds ratio, 3.2; 95% CI, 1.4 to 7.5) and vWF:RCo (odds ratio, 2.1; 95% CI, 0.9 to 4.8) compared with individuals in the lowest quartiles. In individuals with ADAMTS 13 in the lowest quartile, the relative risk of stroke was 1.7 (95% CI, 0.7 to 3.9) compared with the highest quartile. C-reactive protein, ADAMTS 13, and genetic variation did not affect the association between vWF and the relative risk of stroke, whereas blood group did affect the association.Conclusions-vWF antigen and activity are associated with the occurrence of acute ischemic stroke. This relation is unaffected by the severity of the acute-phase response or by genetic variation or degradation.
KW - Adamts13
KW - Hemostasis
KW - Ischemic stroke
KW - von Willebrand factor
U2 - 10.1161/01.STR.0000244767.39962.f7
DO - 10.1161/01.STR.0000244767.39962.f7
M3 - Article
C2 - 16990571
SN - 0039-2499
VL - 37
SP - 2672
EP - 2677
JO - Stroke
JF - Stroke
IS - 11
ER -